Stereoselective sialylation with O-trifluoroacetylated thiosialosides: hydrogen bonding involved?

• Published in: Carbohydrate research Vol. 451; pp. 12 - 28
• Main Authors: Podvalnyy, Nikita M., Malysheva, Nelly N., Panova, Maria V., Zinin, Alexander I., Chizhov, Alexander O., Orlova, Anna V., Kononov, Leonid O.
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 08.11.2017; Elsevier
• Subjects: Biochemistry & Molecular Biology; Burkholderia cenocepacia - chemistry; Chemistry; Chemistry, Applied; Chemistry, Organic; Glycosylation; Hydrogen Bonding; Life Sciences & Biomedicine; Lipopolysaccharides - chemistry; Neuraminic acid; O-trifluoroacetyl group; Physical Sciences; Science & Technology; Sialylation; Stereoisomerism; Supramer approach; Neuraminic acid; O-trifluoroacetyl group; Supramer approach; Glycosylation; Sialylation; Hydrogen bonding; MOLAR-MASS COMPOUNDS; AQUEOUS-SOLUTIONS; SCALE SUPRAMOLECULAR STRUCTURE; SIALIC-ACID; GLYCOSYL DONOR; N-ACETYL; ACETYL-NEURAMINIC ACID; ALPHA-SIALYLATION; BASE CATALYSIS; SIDE-CHAIN CONFORMATION
• ISSN: 0008-6215; 1873-426X
• DOI: 10.1016/j.carres.2017.09.002

A series of novel sialyl donors containing O-trifluoroacetyl (TFA) groups at various positions was synthesized. The choice of protecting groups in sialyl donors was based on hypothesis that variations in ability of different acyl groups to act as hydrogen bond acceptors would influence the supramolecular structure of reaction mixture (solution structure), hence the outcome of sialylation. These glycosyl donors were examined in the model glycosylation of the primary hydroxyl group of 1,2:3,4-di-O-isopropylidene-α-D-galactopyranose in comparison with sialyl donors without O-TFA groups. The presence of O-TFA groups in a sialyl donor strongly affected the outcome of sialylation. Several sialyl donors studied showed promising results: yields of disaccharides can be as high as 86% as can be the stereoselectivities (α/β up to 15:1). The results obtained suggest that varying acyl O-protecting groups in sialyl donor may result in dramatic changes in the outcome of sialylation although further studies are required to dissect the influence of intermolecular hydrogen bonding and intramolecular substituent effects related to variations of electron-withdrawing properties of different acyl groups. [Display omitted] •Varying protecting groups may change solution structure and sialylation outcome.•Influence of O-protecting group pattern on the sialylation outcome was studied.•A series of novel sialyl donors containing O-TFA groups was synthesized.•The presence of O-TFA groups strongly influenced the sialylation outcome.•Combination of O-TFA and O-CA groups is the key to stereoselective sialylation.